Introduction
Over the past few decades obesity has become a major burden on health worldwide. The prevalence of hypertension has increased with a significant increase in the prevalence of overweight and obesity. Recent studies indicate an important role of adipose tissue hormones called adipokines in obesity-associated complications. Apelin has recently been added to the family of adipokines. One of the physiologic functions of the apelin/APJ system is regulation of the cardiovascular function. The aim of this study was to determine the relation of serum apelin to obesity-associated hypertension as well as to myocardial performance.
Patients and methods
The study included 30 obese hypertensive patients, 30 obese nonhypertensive patients, and 25 age-matched and sex-matched controls. In all studied participants we determined the lipid profile, serum insulin, fasting blood glucose level, HOMA-IR, serum apelin, and echocardiographic results of left ventricular systolic and diastolic function.
Results
Higher levels of fasting blood glucose, fasting serum insulin, HOMA-IR, triglycerides, total cholesterol, and low-density lipoprotein were detected in obese hypertensive and nonhypertensive patients. Left ventricular mass index (LVMI) was increased in both obese hypertensive and nonhypertensive patients in comparison with healthy individuals. Left ventricular ejection fraction and E/A ratio were significantly lower in hypertensive obese versus nonhypertensive obese individuals (P = 0.004 and <0.001, respectively), whereas LVMI was higher in hypertensive versus nonhypertensive patients (P < 0.001). Apelin levels were significantly equally higher in obese hypertensive and nonhypertensive patients (6.10 ± 1.88 and 6.40 ± 1.60 ng/ml) compared with controls (4.22 ± 0.86 ng/ml, P < 0.001). In hypertensive obese individuals, serum apelin correlated negatively with left ventricular ejection fraction (P = 0.02) and directly with E/A ratio (P = 0.03).
Conclusion
Apelin levels are significantly higher in obese hypertensive and nonhypertensive patients. This increase might be a compensatory mechanism against myocardial dysfunction with obesity.

Background
Thyroid hormonal disturbance plays an essential role in coronary artery disease (CAD) development and progress. Few studies have detected the relation between percutaneous coronary intervention (PCI), thyroid gland function, and morphology. We aimed to assess the influence of baseline thyroid function tests on the outcome of PCI in euthyroid patients with CAD, and to detect the effect of PCI on the thyroid function and ultrasound features.
Patients and methods
This study included 113 clinically euthyroid patients with stable CAD. Serum free T3, serum free T4, thyroid-stimulating hormone (TSH), thyroid-stimulating hormone index, free T3/T4 ratio, anti-thyroperoxidase (TPO), and high-sensitivity C-reactive protein had been measured before, and then 24 h and 3 months after PCI. The morphology of thyroid was evaluated through thyroid ultrasound before and 3 months after PCI.
Results
One day after PCI, there was a significant increase in serum FT3 and serum FT4 and no significant change in the serum TSH compared with just before PCI (P < 0.001, P = 0.04, P = 0.97, respectively). In addition, there was a significant increase in serum FT3/FT4 ratio compared with just before PCI (P = 0.007). Three months after PCI, there was a significant increase in serum FT4, decrease in serum FT3 returning to baseline, and a significant increase in serum TSH compared with just before PCI (P = 0.42, P < 0.001, P < 0.001, respectively). There was a significant decrease in the serum FT3/FT4 ratio and significant increase in serum thyroid-stimulating hormone index compared with just before PCI ( P ≤ 0.001, P < 0.001, respectively). Higher TSH and measured echogenicity index were independent pre-PCI predictors of unfavorable outcomes after 24 h with cutoff values greater than 0.95 mIU/ml and greater than 1.81, respectively. Lower FT3 and higher FT4 levels were independent pre-PCI predictors of unfavorable outcomes after 3 months with cutoff values less than or equal to 2.95 pg/ml and greater than 1.3 ng/dl, respectively.
Conclusion
A state of euthyroid hyperthyroxinemia was detected 24 h after PCI. A state of thyroid hormone resistance was detected 3 months after PCI. Higher TSH and measured echogenicity index independently predicted unfavorable outcome after 24 h. Lower FT3 and higher FT4 levels independently predicted unfavorable outcomes after 3 months.

Background
Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens; they represent a heterogeneous group of disorders that afflict specific target organs or multiple organ systems. Autoimmune thyroid disease (AITD) is a common organ-specific autoimmune disorder affecting mostly middle-aged women. AITD is a term that includes various clinical forms of autoimmune thyroiditis; among these diseases, Hashimoto's thyroiditis and Graves' disease are the two most common types and share many features immunologically. Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to severe disability and premature mortality. Given the same pathogenic mechanisms, autoimmune diseases tend to cluster together, and hence this study was designed to investigate the relationship between AITD and RA, particularly seropositive versus seronegative subtypes.
Patients and methods
The study included 70 patients with evidence of RA. Their diagnosis was based on the 2010 American College of Rheumatology (ACR)-EULAR classification criteria, and they were subclassified into two groups: group I, comprising 35 patients with seropositive RA (positive to one or both seromarkers), and group II, comprising 35 patients with seronegative RA (negative to both seromarkers). Twenty healthy age-matched and sex-matched controls constituted group III. All of the studied participants underwent detailed history-taking and physical examination, focusing on RA duration of illness, clinical features suggestive of thyroid dysfunction, and disease activity score (DAS28). We determined the complete blood count, erythrocyte sedimentation rate, C-reactive protein, urea, creatinine, alanine aminotransferase, aspartate aminotransferase, thyroid stimulating hormone (TSH), serum total T3 (TT3), serum total T4 (TT4), rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP), anti-thyroid peroxidase (anti-TPO), thyroglobulin Ab, and TSH receptor antibody (TRAb) levels, and also performed a neck ultrasound.
Results
It was found that erythrocyte sedimentation rate, C-reactive protein, RF, and anti-CCP were significantly higher in RA patients versus controls, particularly in seropositive versus seronegative patients. No significant difference was found between the studied groups as regards TSH, T3, and T4 levels; however, hypothyroidism was found to be more common than hyperthyroidism in RA patients (29 vs. 3% in group I and 9% in group II). Anti-TPO and antithyroglobulin were significantly higher in RA patients versus controls (P < 0.001) and specifically in seropositive (1301.9 ± 1716.0 and 1750.0 ± 1866.2, respectively) versus seronegative patients (799.4 ± 1597.7 and 898.1± 988.11, respectively). TRAbs were detectable in a small subset of RA patients (6% regardless of the serostatus) with significant difference between patients and controls (P = 0.006). Ultrasonographic features of thyroiditis were significantly evident in RA patients versus controls (P = 0.001). A positive correlation was found between RA autoantibodies (RF and anti-CCP) and thyroid autoantibodies (mainly anti-TPO and TRAbs) (P = 0.007, 0.012, 0.004, and 0.035, respectively).
Conclusion
Thyroid dysfunction and AITD are common in RA patients, with hypothyroidism being the most common disorder, which is prevalent in 29% of patients regardless of their serostatus. This association was independent of disease activity assessed by DAS28. Increased incidence of thyroid autoimmunity was seen in seropositive RA versus seronegative RA patients, as evidenced by higher levels of thyroid autoimmune markers in the former. TRAbs were detectable in a small subset of patients with RA.

Background
Paralleling the increasing prevalence of obesity in the Egyptian population, metabolic syndrome and liver steatosis are also on the rise. Body composition measurement is used to describe the percentages of fat, bone, water, and muscle in human bodies. The available classic weight loss treatments such as low-calorie diet, exercise, behavioral modification, and pharmacotherapy usually achieve only limited weight loss. The BioEnterics Intragastric Balloon (BIB) is an endoscopic liquid-filled device for the treatment of obesity.
Aim
The aim of this study was to examine the safety of BIB insertion in a group of obese middle-aged Egyptian women treated with intragastric balloon to induce weight loss for 6 months and report its effect on their anthropometric measurements, body composition, fatty liver, and comorbidities.
Patients and methods
During the period from February 2012 until August 2013, 47 consecutive middle-aged female patients were enrolled for BIB insertion. Inclusion criteria were mainly based on the BMI (≥30.0 kg/m 2 ) and on associated comorbidities. Apart from physical and anthropometric evaluation, body composition analysis was performed using a bioelectrical impedance analyzer to estimate fat mass, body fat percentage, and fat-free mass. The Adult Treatment Panel III criteria were used to diagnose metabolic syndrome, and ultrasound evaluation of the liver for the presence and grade of steatosis was performed. BIB placement was carried out after diagnostic endoscopy, under intravenous conscious or unconscious sedation.
Results
The total percentage of complications from BIB insertion was 12.8%, which were mostly mild and reversible. Three (6.4%) patients had their gastric balloon removed early (two voluntarily and one due to de-novo peptic ulcer) and were excluded from the study, whereas the remaining 44 patients continued their 6-month therapy duration. Overall, BIB insertion significantly reduced weight from a mean value of 96.82 ± 14.18 kg at baseline to 83.45 ± 12.03 kg after 6 months (P < 0.001). The mean value for the amount of weight lost at endpoint was 13.36 ± 3.29 kg, whereas the mean value for BMI lost at the time of BIB removal was 5.12 ± 1.20 kg/m 2 , which was a significant reduction compared with baseline values (P < 0.001). No significant change occurred in the liver size over the 6-month study period (P = 0.12), whereas a significant decrease in the grade of steatosis was noted. Body fat mass and body fat percentage with bioelectrical impedance analyzer were significantly reduced (P < 0.001). However, there was also a significant decline in fat-free mass (P < 0.001). Significant favorable changes in the biochemical markers of metabolic syndrome, homeostasis model assessment of insulin resistance index, and liver profile also occurred. An overall 4.6% of patients showed resolution, whereas 31.8% showed improvement in the features of metabolic syndrome.
Conclusion
This study provides anthropometric, biochemical, and body composition evidence on significant improvement in metabolic syndrome, obesity-associated comorbidities, and fatty liver after weight loss induced by the minimally invasive and relatively safe technique. However, it is recommended to continue a weight-reducing diet after BIB removal for achieving long-term effectiveness and to add exercise programs to dietary restriction for promoting more favorable change in body composition.

The role of genetic polymorphism of β3-adrenergic receptor in the susceptibility to diabetes and its related disorders: a case–control study on Egyptian populationNeveen S.E.D Hemimi, Mona M Abdelsalam, Lamis M Tawfik, Marwa M KhalilMay-August 2017, 3(2):39-45DOI:10.4103/ejode.ejode_8_17

Background The β3-adrenergic receptor (β3-AR) is mainly expressed in adipose tissue and plays an important role in lipid metabolism and metabolic rate by mediating lipolysis and thermogenesis. It has been suggested that the Trp64Arg (T→C) polymorphism in the β3-AR gene affects fat accumulation and/or impairment of lipid and carbohydrate metabolism.
Objective The aim of this study was to investigate whether common polymorphism (Trp64Arg) of β3-AR gene has a role in the apparent susceptibility to type 2 diabetes mellitus (DM) and its related disorders in the Egyptian population.
Patients and methods One hundred and thirty five healthy controls and 123 individuals with type 2 DM were enrolled in the study. The β3-AR Trp64Arg polymorphism was identified using restriction fragment length polymorphism PCR of peripheral blood DNA samples. Analysis of data was performed using SPSS program 11.
Results Allele frequency for C was 23.2% in the diabetic group compared with 12.2% in the control group. The carriers of XC genotype (TC and CC) were at high risk of developing type 2 DM (odds ratio=2.8; 95% confidence interval=1.6–4.9) when compared with the carrier of TT genotype. Furthermore, they were at much higher risk of developing its related disorders such as central obesity, dyslipidemia, and hypertension (odds ratio=2.8; 1.8, 1.5, 2.2, and 2.7 for BMI, waist–hip ratio, triglycerides, high-density lipoprotein, and hypertension, respectively).
Conclusion The prevalence of Arg64 allele of the Trp64Arg polymorphism in the β3-AR gene is a risk factor for type 2 DM and its related disorders in the Egyptian population.

Objective
The aim of this study was to evaluate vitamin D level in type 2 diabetic patients before and after treatment with pioglitazone and assess any possible relationship with type 2 diabetic patients who are pioglitazone naive.
Participants and Methods
The study included 50 female participants; of them, 20 were healthy female participants who served as controls and 30 were pioglitazone-naive diabetic patients. All individuals were subjected to history taking and clinical examination, including fasting blood sugar, 2 h postprandial, glycosylated hemoglobin (HbA1c), lipid profile test (total cholesterol, HDL, LDL, triglycerides), kidney function tests (serum creatinine and calculated glomerular filtration rate), and evaluation of serum calcium, phosphorus, and alkaline phosphatase and serum 25-hydroxy vitamin D (by enzyme linked immunosorbant assay) before (basal) and after 3 months of treatment with pioglitazone.
Results
There was an nonsignificant elevation of vitamin D in group 2b (diabetic patients after using pioglitazone for 3 months), in comparison with vitamin D level in group 2a (diabetic patients before using pioglitazone) (P = 0.117). Vitamin D levels were found to be inversely associated with HbA1c levels in type 2 diabetic patients (P = 0.000 linear regression analysis); it was also found to be inversely associated with fasting and 2 h postprandial blood sugar levels (P < 0.000).
Conclusion
Vitamin D could impact glycemic control in terms of the inverse relation of vitamin D with HbA1c%, and at the same time poor glycemic control could impact vitamin D status in uncontrolled diabetic patients. Thiazolidinediones do not have significant effect on vitamin D level in female diabetic patients.

Background Obesity is considered to be a worldwide health problem. Obese individuals are at a high risk of developing dyslipidemia, hypertension, impaired glucose tolerance, insulin resistance, and consequent increase of the risk of metabolic and cardiovascular diseases. In obesity, elevated insulin resistance is observed, which may be associated with disturbances in zinc status in the body. The few studies concerning the status of zinc and its relationship with insulin resistance in obese children and adolescents have brought inconclusive results.
Aims The aims of this work were to study the level of serum zinc in obese children and adolescents and to evaluate its potential relation to obesity, insulin resistance, and lipid profile.
Patients and methods Thirty obese children and adolescents and 30 healthy controls aged 5–19 years were recruited for the study. Lipid profile, serum zinc, fasting plasma glucose, and fasting insulin were measured. Insulin resistance was calculated according to the homeostatic model of assessment for insulin resistance and quantitative insulin-sensitivity check index.
Results Obese individuals had significantly higher serum triglycerides, total cholesterol, low-density lipoprotein cholesterol, fasting plasma glucose, fasting blood insulin, and homeostatic model of assessment for insulin resistance, whereas high-density lipoprotein cholesterol and quantitative insulin-sensitivity check index were significantly lower in obese children than in healthy controls (all P<0.05). The serum concentration of zinc was significantly lower in obese individuals compared with control. There was a positive significant correlation between serum zinc level and high-density lipoprotein (r=0.511, P<0.05).
Conclusion Obese children and adolescents have a poorer zinc status than children and adolescents of normal weight, which may affect lipid profile.

Background
Diabetic nephropathy (DN) is the leading cause of renal failure. Diabetic patients with microalbuminuria typically progress to proteinuria and overt DN. Similar to other microvascular complications of diabetes, there are strong associations between glucose control (as measured using HbA1c) and the risk of developing DN. Apelin (APLN), a peptide first isolated from bovine stomach tissue extracts, is the endogenous ligand for the G-protein-coupled APJ receptor that is expressed at the surface of some cell types. APLN and APJ are widely expressed in homogenates from animal organs in a pattern shared with angiotensinogen and the angiotensin receptor. APLN is widely distributed in the central nervous system and periphery, especially in the heart, kidney, lung, and mammary glands. The APLN–APJ system may be involved in the pathogenesis of DN, which may play a renoprotective role partially by antagonizing the angiotensin II–ATIR pathway.
Aim The aim of this study was to investigate the relation between serum APLN and different grades of DN in type 2 diabetic patients.
Patients and methods
This study was conducted on 150 diabetic patients and 20 controls selected from the inpatient department and outpatient clinics of the Internal Medicine Department in Menoufia University Hospital. The selected participants were divided into four groups: group 1 included 20 healthy controls; group 2 included 50 type 2 diabetes mellitus (T2DM) patients with normoalbuminuria; group 3 included 50 T2DM patients with microalbuminuria; and group 4 included 50 T2DM patients with macroalbuminuria. Members of the study groups were subjected to thorough history taking with special emphasis on age, sex, and duration of diabetes mellitus. Investigations included liver profile, complete blood count, fasting and 2 h postprandial plasma glucose, glycosylated hemoglobin (HbA1c), complete urine analysis, kidney function tests (blood urea nitrogen and serum creatinine), urine albumin/creatinine ratio, estimated glomerular filtration rate, and serum APLN.
Results
Serum APLN was significantly higher in group 4 compared with the other groups, in group 3 compared with groups 1 and 2, and in group 2 compared with group 1. There was a significant positive correlation between serum APLN and serum creatinine, urine albumin/creatinine ratio, and HbA1c. Further, there was a significant negative correlation between serum APLN and estimated glomerular filtration rate in the studied diabetic patients. There was no correlation between serum APLN and BMI in diabetic patients.
Conclusion
From this study, we can conclude that serum APLN is significantly higher in patients with DN compared with diabetic patients without nephropathy, and there is a positive correlation between serum apelin and the degree of DN. Thus, APLN may play an important role in the development of DN.

Introduction
The early prediction and prevention of cardiovascular disease risk factors is highly important in chronic kidney disease (CKD) patients. The plasma level of omentin was found to be associated with different disorders such as insulin resistance, diabetes mellitus, obesity, endothelial dysfunction, and atherosclerosis. The aim of the study was to clarify the influence of changes in levels of circulating omentin-1 on insulin resistance in CKD patients with and without type 2 diabetes mellitus.
Participants and methods
Seventy-eight patients were enrolled in this cross-sectional study: 23 patients with CKD on conservative treatment, 35 patients on maintenance hemodialysis, and 20 healthy volunteers. Serum concentrations of omentin-1 were determined with an enzyme-linked immunosorbent assay kit.
Results
Significant difference in plasma omentin-1 level was noticed between diabetic patients and nondiabetic patients in both the predialysis group and the hemodialysis (HD) group. There was also a significant difference in plasma omentin-1 level between nondiabetic patients in the predialysis group and the HD group and between diabetic patients in the predialysis group and hemodialysis group. There were significant negative correlation between plasma Omentin-1 level (ng/ml), fasting insulin level (mIU/ml), HOMA-IR and eGFR (ml/min/1.73m 2 ) while significant positive correlation with IL-6 (pg/ml) and hsCRP (mg/l).
Conclusion
Plasma omentin-1 concentration was higher in CKD patients. In addition, there was an association between omentin-1 and insulin resistance in hemodialysis patients, which may be considered a cardiovascular risk factor in CKD patients.

Objective
The aim of the present study was to evaluate the relationship between serum testosterone concentration and carotid atherosclerosis in elderly men.
Participants and methods
The current study included 40 participants who were classified into two groups; the first group comprised 30 elderly healthy men (the case group) and the second group comprised 10 young males (the control group). Serum level of total testosterone was measured using a commercial immunoassay kit cobas testosterone II; sex hormone binding globulin (SHBG) was measured using a commercial immunoassay kit cobas. SHBG and free androgen index (FAI) were calculated by dividing the total testosterone value by SHBG value and then multiplying it by 100 [total testosterone (nmol/l)/SHBG (nmol/l)Χ100%]. Ultrasonographic measurement of carotid intima-media thickness (IMT) was also carried out.
Results
Total testosterone level was significantly lower in the case group than in the control group (t = 5.354, P < 0.001). SHBG was significantly higher in the case group than in the control group (t = 4.796, P < 0.001). FAI was significantly lower in the case group than in the control group (z = 4.686, P < 0.001). IMT was significantly higher in the case group than in the control group (t = 3.513, P = 0.001). As regards the number of plaques, 10 men participants (33.3%) from the case group did not have any plaques, 13 (43.3%) had one plaque, and seven (23.3%) had two plaques; however, in the control group, nine participants (90%) did not have any plaques and only one (10%) had one plaque; therefore, the case group had significantly higher number of plaques than did the control group (z = 3.007, P = 0.003). There was a significant negative correlation between total testosterone and SHBG (R = −0.856, P < 0.001), a significant positive correlation between total testosterone and FAI (R = 0.957, P < 0.001), and a significant negative correlation between testosterone and both IMT (R = −0.501, P = 0.005) and number of plaques (R = −0.358, P = 0.52). SHBG was negatively correlated with FAI (R = −0.845, P < 0.001) but positively correlated with both IMT (R = 0.392, P = 0353) and the number of plaques (R = 0.032, P = 0.056). There were significant negative correlations between FAI and both IMT (R = −0.601, P < 0.001) and the number of plaques (R = −0.461, P = 0.010). IMT was positively correlated with the number of plaques (R = 0.760, P < 0.001).
Conclusion
These findings suggest that normal physiologic testosterone levels may help to protect men from atherosclerosis. In elderly men, low plasma testosterone is associated with elevated carotid IMT. A negative correlation has been demonstrated between endogenous testosterone levels and IMT of the carotid arteries. These findings suggest that men with lower levels of endogenous testosterone may be at a higher risk for developing atherosclerosis.

Background Nesfatin-1 is a newly found anorectic neuropeptide with potent metabolic regulatory effects, whose peripheral levels are shown to be elevated in diabetes. It is a newly discovered hypothalamic neuropeptide that regulates appetite. Its discovery has generated great interest in the scientific community because of its implication in energy and glucose homeostasis. Nesfatin-1 is an amino-acid peptide originating from the cleavage of nucleobindin2. It has a molecular weight of 9.8 kDa and the half-life of nucleobindin2 mRNA is ∼6 h. Interestingly, nesfatin-1 is also expressed in pancreatic β-cells, where it is localized with insulin in secretion vesicles. The structure of nesfatin-1 is also tripartite; the segment starting from the N-terminal end and going up to 23 amino acids is called N23, the middle segment covering the amino acids from 23 to 53 is called M30, and the segment from the 53rd to 82nd amino acids toward the carboxyl terminus is called C29.
Objective We compared serum nesfatin-1 in patients with type 2 diabetes with evidence of diabetic kidney disease (DKD) [urinary albumin–creatinine ratio (UACR) >300 mg/day or reduced estimated glomerular filtration rate (eGFR) <60 ml/min] with patients newly diagnosed with type 2 diabetes and who had no evidence of DKD (UACR<30 mg/day) and a control group of healthy nondiabetic individuals.
Patients and methods Ninety patients attending the outpatient clinics at Alexandria Main University Hospital and Alexandria Police Hospital, Egypt, were enrolled in this cross-sectional study to determine the association of serum level of nesfatin-1 and DKD in patients with type 2 diabetes. They were divided into three groups: group I included 30 type 2 diabetic patients with DKD. Group II included 30 type 2 diabetic patients without DKD. Group III included 30 nondiabetic healthy controls matched for age and sex with group I. Assessment included a thorough assessment of history, complete clinical examination, neurological examination, fundus examination, and laboratory investigations including metabolic profile and plasma nesfatin-1 by enzyme-linked immunosorbent assay.
Results The study showed a statistically significant difference between the three studied groups in terms of age (P<0.001), HbA1c and fetal bovine serum (P≤0.001), fasting insulin level (P=0.022), blood urea (P<0.001), serum creatinine (P<0.001), eGFR (P<0.001), and UACR (P<0.001). The difference between the three groups studied was not significant in serum nesfatin-1 (P<0.564). The mean peripheral concentrations of nesfatin-1 were not significantly higher in patients with diabetes who had evidence of DKD compared with newly diagnosed type 2 diabetic patients who had no evidence of DKD (P<0.001).
Conclusion Serum nesfatin-1 was not significantly higher in albuminuric type 2 diabetic patients compared with normoalbuminuric patients. Serum nesfatin also did not correlate with eGFR and creatinine in the different groups studied. Serum nesfatin-1 may not be useful as an early marker of DKD instead of albuminuria. More studies are needed to identify the role and the significance of nesfatin in diabetic patients.

Background
The Child-Turcotte-Pugh (CTP) score inaccurately predicts survival in patients with chronic liver disease, including hepatocellular carcinoma (HCC), yet remains the standard tool for assessing hepatic reserve and guiding therapeutic decisions. CTP scoring relies on objective laboratory values for albumin, bilirubin, and prothrombin time and subjective clinical grading of hepatic encephalopathy and ascites. As liver production of insulin-like growth factor-1 (IGF-1) is significantly reduced in patients with cirrhosis, we hypothesized that IGF-1 could be a valid surrogate for hepatic reserve to replace the subjective parameters in CTP scores.
Materials and methods
We prospectively enrolled patients and collected data and retrospectively tested plasma IGF-1 levels in four independent cohorts: two HCC cohorts from the USA [n = 310 (training set) and n = 99 (validation set 1)]; one HCC cohort from Korea [n = 188 (validation set 2)]; and one cirrhosis cohort from Egypt [n = 71 (validation set 3)]. Recursive partitioning identified within the training set three optimal IGF-1 ranges that correlated with survival: >50 ng/ml = 1 point; 26-50 ng/ml = 2 points; and <26 ng/ml = 3 points. We modified the CTP score by replacing ascites and encephalopathy grading with IGF-1 values, subjected both the resulting IGF score and the CTP score to log-rank analysis, and quantified the prognostic values with C-statistics to compare the scores' performance in all cohorts.
Results
The IGF score was significantly more accurate in predicting survival and improved the stratification of all CTP classes in the training and validation cohorts.
Conclusion
The new IGF score is simple and blood-based, and validated well on multiple independent HCC cohorts. It could identify a subpopulation of patients who may benefit from active therapy because of their preserved hepatic reserve, as distinct from patients for whom therapy can be deferred or avoided.

Introduction
There is growing evidence that some cases of chronic idiopathic urticaria are associated with various autoimmune diseases such as thyroid autoimmunity. The association between chronic urticaria (CU) and thyroid disorders has been a subject of controversy. Some reports link CU with hyperthyroidism or hypothyroidism. The frequency of thyroid antibodies in patients with chronic idiopathic urticaria reported in 2009 was 30%, which is higher than that previously reported.
Objective
This is a case-control study that aimed to detect the presence of markers of thyroid autoimmunity (thyroid autoantibodies with or without underlying abnormal thyroid functions) among a cohort of autologous serum skin test (ASST)-positive patients with CU in comparison with ASST-negative CU patients as well as with healthy controls, and correlating it to the severity of urticaria symptoms.
Patients and methods
This study was carried out on 80 CU patients attending the Allergy and Immunology Clinic of Ain Shams University Hospitals. CU was diagnosed on the basis of the appearance of continuous recurrent hives for more than 6 weeks. The patients were subdivided into the following groups: group A - 40 CU patients with positive ASST; group B - 40 CU patients with negative ASST. In addition, 40 healthy individuals were included in this study as healthy controls. History and general examination were conducted to all study grouos. Assessment of the Urticaria Activity Score-7 and laboratory investigations including those for complete blood count, erythrocyte sedimentation rate, thyroid function, thyroid Abs, namelyantimicrosomal antibody and antithyroglobulin antibody and total immunoglobulin E (IgE), were done.
Results
Comparison between the three groups showed that antithyroglobulin antibody was highly statistically significant in group A than in both group B and healthy controls. Moreover, antimicrosomal antibody was also found to be of higher statistical significance in group A than in both group B and healthy controls. Although total IgE had no statistical significance between groups A and B, total IgE was found to be statistically significantly higher in group B than in healthy controls. Level of thyroid stimulating hormone was higher in group A than in controls, and free T3 was lower in group A than in group B.
Conclusion
We suggest that thyroid diseases have a role in CU, which was confirmed by a higher level of thyroid antibodies in the ASST-positive group than in ASST-negative patients and healthy controls.

Introduction Vitamin D is one of the important hormones involved in Ca homeostasis. It is also essential for the prevention of osteoporosis and fractures. Vitamin D is important for maintaining many physiologic functions, such as optimal balance, muscle strength, and innate immunity. Vitamin D deficiency is associated with an increased risk for several types of cancer, as well as autoimmune and cardiovascular disorders. As the influence of diet on vitamin D status is minimal and most circulating vitamin D is derived from exposure to sunlight, elderly populations are greatly affected; they have marked limitations that hinder their exposure to sunlight as well as their feeding and nutritional habits.
Objectives of the study The aim of this study was to assess vitamin D status in Egyptian geriatric, homebound, nursing home residents, and ambulatory elderly individuals.
Patients and methods This study was carried out on 90 elderly male and female individuals divided into three groups: the first group included 30 homebound elderly individuals, the second group included 30 elderly individuals living in nursing homes, and the third group included 30 community-dwelling ambulatory elderly individuals.
Results There were high statistically significant difference in the vitamin D levels between the groups studied, being the highest in group III, 158 (18–240) nmol/l, and the lowest in group II, 16 (4–194) nmol/l. Statistically significant differences were found in sun exposure, with good exposure in 60% of the individuals in group III. There were also statistically significant differences in the intake of vitamin D in diet, with good intake in 64.30% of the individuals in group III. Also, we found the highest waist circumference in group II (98.68±20.73 cm). Vitamin D showed a significant positive correlation with serum calcium in group II (ρ=0.199) and a positive correlation with aspartate transaminase (AST) in group III (ρ=0.418).
Conclusion Elderly Egyptian individuals in nursing houses are at risk of developing vitamin D deficiency because of lack of exposure to sunlight, dietary problems, and or central obesity.

Introduction
Chronic kidney disease (CKD) is a worldwide disease that is classified into five stages according to the glomerular filtration rate and presents through a variety of symptoms and signs. Anemia is one of the first signs of kidney dysfunction. The most common causes of anemia in CKD are erythropoietin (EPO) hormone deficiency and iron deficiency. Anemia and hyporesponsiveness to erythropoietin-stimulating agents (ESAs) are commonly observed in CKD patients and are associated with increased morbidity, mortality, and a significant healthcare economic burden. Although testosterone deficiency is a prevalent condition in men with CKD, it has so far received relatively little attention in practice. Testosterone stimulates erythropoiesis through the production of hematopoietic growth factors and possible improvement of iron bioavailability.
Aim
The aim of this study was to evaluate serum testosterone levels in patients on maintenance hemodialysis (MHD) and correlate its level with anemia and response to ESAs therapy.
Patients and methods
This study included 40 male patients from dialysis units, where they were divided equally into group A, group taking ESAs, and group B, group not taking ESAs (EPO-naive group). Another 20 men were included in group C (control group). All groups were subjected to a full assessment of history, full clinical examination, and laboratory investigations to exclude all possible causes of anemia.
Results
This study showed that in group A, 75% of the participants were anemic, whereas in group B, 100% of the participants were anemic, with a higher degree of anemia. The testosterone level was slightly higher in group B than group A; despite being within the normal range, it was relatively deficient on the basis of the age of the participants in the control group.
Conclusion
Testosterone deficiency is a prevalent condition in CKD that starts at an earlier age than the normal population. It is an evident independent cause of anemia in EPO-naive CKD patients and is a possible cause of resistance of ESAs in CKD patients; still, the most important causes of anemia in CKD are EPO and iron deficiency.

Context
Android obesity is considered an important predictor of increased mortality and morbidity from diabetes mellitus and cardiovascular disorders.
Aim
Our research was conducted to assess the level of serum visfatin in android obesity and its relation to anthropometric and biochemical parameters in adults with android obesity.
Patients and methods
This study was conducted on 136 patients recruited from the outpatient obesity clinic of Specialized Medical Hospital, Mansoura University. The patients were divided into two groups: group I consisted of 65 control nonobese individuals, and group II consisted of 71 obese individuals with android obesity. The obese patients were subdivided into obese diabetic patients (35 patients) and obese nondiabetic patients (36 patients). All participants were subjected to thorough history taking, full clinical examination, and anthropometric measurements to assess body mass index and waist circumference. The changes that appeared in the carbohydrate metabolism were interpreted according to the criteria from the glycometabolic classification of WHO. Plasma glucose levels, lipid profile, and serum visfatin were measured.
Results
Our study demonstrated a significant elevation of visfatin (P≤0.001) in obese individuals (37.6; 20.7–65.9) compared with that in lean patients (15.3; 7.5–20). Additionally,visfatin levels were higher in the diabetic obese subgroup (45.5; 33.7–65.9) than in the nondiabetic obese subgroup (32; 20.7–46.5). Furthermore, visfatin was positively correlated to blood glucose in the obese group, which suggests a role of visfatin in glycemic control. A significant correlation between visfatin and lipid profile was demonstrated, which may suggest a role for visfatin in lipid homeostasis.
Conclusion
Serum visfatin was elevated in patients with android obesity, with more significant elevation in patients with android obesity with type 2 diabetes mellitus. It showed potential to be used as a marker of metabolic syndrome as it had a strong relation to android obesity.

Introduction
Frailty is a common and growing multidimensional health and social care challenge across the world. Diabetes mellitus (DM) is one of the most important causes of morbidity and mortality in Egypt. Frailty and diabetes are inter-related. In addition, diabetes causes early-onset frailty. In this study we aimed to determine the frailty index in elderly men with type 2 DM and compare it with that in pre-elderly diabetic patients and age-matched healthy controls.
Materials and methods
Seventy male participants were included in the present study and were divided into three groups. Group I comprised 20 healthy men aged 65-75 years who were considered the control group; group II comprised 25 patients aged 50-64 years with type 2 DM; and group III comprised 25 patients aged 65-75 years with type 2 DM. Patients on insulin therapy and those with hypogonadism or hypothyroidism were excluded from the study. Frailty index was determined for all participants using Fried's five phenotypic parameters. Patients were considered frail if they fulfilled more than or equal to three parameters, prefrail if they fulfilled one to two parameters, and nonfrail if they fulfilled none of the parameters. Data were collected, analyzed, and compared between groups I and III and between groups II and III. Further, frailty index was correlated with the duration of DM and the degree of glycemic control.
Results
Seventy patients were divided into three groups. The mean age in group I was 68.50 ± 1.90 years, that in group II was 58.24 ± 4.34 years, and that in group III was 68.60 ± 2.43 years. Regarding the frailty index, in group I 17 patients (85%) were nonfrail, three (15%) were prefrail, and none were frail; in group II, four patients (16%) were prefrail, 21 (84%) were frail, and none were nonfrail; and in group III, three patients (12%) were prefrail, 22 (88%) were frail, and none were nonfrail. A statistically significant difference was noted between groups I and III, whereas no significant difference was noted between groups II and III. A significant positive correlation was found between the frailty index score and duration of diabetes and degree of glycemic control in groups II and III.
Conclusion
Diabetes and frailty are causally related. Diabetes is associated with frailty at earlier age. The duration of diabetes and degree of glycemic control correlate with the severity of frailty in both elderly and pre-elderly diabetic patients.

Background Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in adult women, and is emerging as a common cause of menstrual disturbance in the adolescent population. Insulin resistance, which is considered one of its underlying causes, has increased markedly in the past decade, placing more adolescent girls at risk for PCOS and its complications. Anti-Mullerian hormone (AMH) is secreted by the granulose cells of ovarian follicles and correlated with the count of small antral follicles and it is expressed throughout folliculogenesis.
Objective This study aimed to evaluate AMH in Egyptian women with PCOS and to determine whether it might serve as a prognostic marker for treatment efficacy with metformin.
Patients and methods This study included 30 women with PCOS (group 1) and 30 healthy women without PCOS (group 2). AMH was measured in both groups, and before and after treatment with metformin (2550 mg) for 3 months in group 1.
Results AMH levels were higher in PCO groups before (3.54±0.58 ng/ml) and after treatment (2.79±0.39 ng/ml) than the control group (2.14±0.49 ng/ml), with P value less than 0.01. In the PCO group, it was higher before (3.54±0.58 ng/ml) than after treatment (2.79±0.39 ng/ml), with P value less than 0.01.
Conclusion AMH is higher in PCO patients and its levels decrease significantly with the insulin sensitizer metformin, and it can be used as a marker for treatment efficacy with metformin.

Background
Diabetes mellitus is a major contributor to morbidity and mortality worldwide. A marked variability in the application of preventive and therapeutic strategies was documented. Good quality of care is associated with lower burden of complications.
Study objectives
The present study was conducted to assess the quality of medical care provided to type 2 diabetic patients attending the internal medicine outpatient clinic in Alexandria Main University Hospital.
Patients and methods
A cross-sectional survey was conducted on 490 type 2 diabetic patients. Patients were interviewed using a structured questionnaire containing data on personal and sociodemographic characteristics as well as their self-care practices. Records of interviewed patients for a set of performance measures for diabetes care during the last year were reviewed. Weight, height, and blood pressure were measured and a series of laboratory investigations were carried out in order to assess the outcome of diabetes care.
Results
The study included 490 diabetic patients, of whom 281 (57.3%) were male patients. Their mean age was 53.62 ± 10.72 years. The duration of diabetes among the studied patients ranged from 1 to 22 years, with a mean of 9.54 ± 4.78 years. Nearly one-third of them were not compliant with antidiabetic treatment; 44.1% were current smokers and 82% of them had never practiced physical exercise before. In the previous 3 months, glycosylated hemoglobin was ordered for only 60.8% of the studied patients. In the last year, foot and fundus examinations were carried out for nearly two-third of the studied patients (68.2 and 64.5%, respectively). Moreover, only 12.5, 26.1, and 38.5% of patients were investigated for microalbuminuria, serum creatinine, and blood lipids, respectively. Uncontrolled hyperglycemic state was diagnosed in a vast majority of cases (99.2%). Moreover, 78.6% were obese and 82% had hypertriglyceredemia.
Conclusion
Intermediate outcome measures – namely, poor glycemic control and high prevalence of obesity and hypercholesterolemia – denote suboptimal medical care and/or poor compliance of patients with self-care management practices. In order to improve quality of care of type 2 diabetes aiming at reducing the incidence of complications, improving outcome, and improving the quality of life of patients, multilevel intervention plan should be carried out.

Context
Diabetic neuropathy is one of the commonest long-term complications of diabetes seen in routine healthcare and considered the most common cause of peripheral neuropathy in developed world.
Aim
The aim of our work was to measure advanced glycation endproducts (AGEs) and their receptors (RAGEs) in diabetic peripheral neuropathy (DPN), both painful and painless DPN.
Patients and methods
Our study was conducted on 50 type 2 diabetes mellitus patients with peripheral neuropathy, divided into two subgroups: the first group included 25 patients with painful DPN and the second group included 25 patients with painless DPN. Moreover, a third group included 20 diabetic patients without peripheral neuropathy, and a fourth group that included 20 healthy participants. All groups were subjected to full history taking and clinical examination, anthropometric parameters, the calculation of neuropathy disability score, and nerve conduction studies (peroneal, sural, and tibial nerves). Laboratory investigations included serum AGEs and RAGEs.
Results
Our study demonstrated that hemoglobin A1c, AGE, and RAGE showed statistically significant difference between the studied groups. Hemoglobin A1c was significantly high in both neuropathic and diabetic groups in comparison with control. Regarding AGE, it was statistically higher in neuropathic group than in control (P<0.011). On the contrary, RAGE was significantly higher in both neuropathic and diabetic groups rather than control (P<0.02). Although the neuropathic group has higher levels of AGE and RAGE than diabetic group, the difference was statistically nonsignificant. Significant difference was found between studied groups regarding nerve conduction studies of sural and tibial nerves. Statistically significant difference was found in the parameters of nerve conduction studies between neuropathic group and both non-neuropathic diabetic and control groups.
Conclusion
Our study concluded that AGE and RAGE are significantly higher in diabetic patients with neuropathy versus control, with more elevation in neuropathic group than in diabetic without neuropathy.

Objective This study aimed to evaluate the effectiveness and safety of insulin glargine in combination with glimepiride treatment in daily practice in patients who failed premixed insulin with or without oral antidiabetic (OAD) regimen.
Patients and methods This 6-month, prospective, multicenter, observational study conducted in Egypt included adult patients with type 2 diabetes mellitus on premix with or without OAD (glimepiride plus metformin), with glycated hemoglobin (HbA1c) greater than 8.5% and for whom the investigator decided to switch to insulin glargine in addition to glimepiride. Overall, three mandatory visits (baseline, 3 months, and 6 months) and seven phone calls were performed by the investigator for each eligible patient. Patients were assessed according to the value of HbA1c and fasting blood glucose (FBG).
Results At the end of this study, the results showed effectiveness of combining insulin glargine plus glimepiride in reducing the mean baseline level of HbA1c% by 1.79 and 2.5% at visit 2 (week 12) and visit 3 (week 24), respectively (P<0.001). The percentage of patients reaching target HbA1c less than 7% in visit 2 (week 12) and visit 3 (week 24) was 5 and 24.3%, respectively. They also showed a significant reduction (P<0.001) in the mean FBG at visit 2 (week 12) and visit 3 (week 24) of 97.44 and 104.4 mg/dl, respectively, whereas the mean percent reductions were 44.37 and 47.54%, respectively. The percentage of patients who reaching FBG less than or equal to 100 mg/dl was 26.7 and 32.2%, in visit 2 (week 12) and visit 3 (week 24), respectively. There was no significant change in mean body weight between baseline and visit 3 (P>0.05). The mean 2-h postprandial blood glucose level was decreased significantly (P<0.001) at visit 2 to 171.93±68.2 mg/dl and at visit 3 to 155.88±56.61 mg/dl. The mean reductions of 2-h postprandial blood glucose at weeks 12 and 24 were 140.8 and 156.8 mg/dl, respectively, and the mean percentage reductions were 45 and 50.1%, respectively.
A total of 50 adverse events were reported by 41 patients during the study. The most frequently reported adverse event was hypoglycemia, which included 37 episodes reported by 31 patients, where nocturnal hypoglycemia was represented in 12 episodes, with percentage of 32.4%.
Conclusion The results showed that a combination therapy of insulin glargine and glimepiride improved glycemic control in patients with type 2 diabetes mellitus, who failed premixed with or without OAD (glimepiride plus metformin). In addition, safety analysis showed high patient tolerability to glargine and glimepiride regimen.

Introduction
Aging results in chronic low-grade inflammation that is associated with an increased risk for disease, poor physical functioning, and mortality. The biomarkers that are mostly related to inflammation such as tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) are created to stimulate and activate the immune system in response to inflammation. Strategies that reduce age-related inflammation may improve the quality of life in older adults. The benefits of regular exercise for the elderly are well established, whereas less is known on the impact of low-intensity resistance exercise on this chronic low-grade inflammation in the elderly.
Aim of the study
To study the level of TNF-α and CRP before and after programmed resistance exercise in Egyptian elderly individuals.
Patients and methods
Thirty healthy elderly individuals aged 60 years or older, of both sexes, participated in 4 weeks of resistance exercise training (RET). Circulating levels of TNF-α and CRP were measured before and after the exercise training.
Results
This study found that both inflammatory markers, TNF-α and CRP, were statistically significantly decreased (P = 0.036, 0.009), respectively, in comparison with the previous starting level measured before the exercise in the same individuals.
Conclusion
There was a negative correlation between TNF-α and CRP levels and the RET, which indicated that RET represents a low-cost strategy that may reduce age-related inflammation and may thus improve the quality of life in older adults.

Introduction
Type 2 diabetes mellitus (T2DM) is a group of pandemic debilitating metabolic diseases featuring chronic hyperglycemia that results from defective insulin secretion and/or insulin actions. Dame and Sutor reported that diabetic patients are prone to thrombocytosis through a complex interplay of mechanisms. Therefore, the aim of our work is to evaluate serum sclerostin levels in patients with T2DM and to analyze the relationships among sclerostin, bone mineral density (BMD), bone metabolism, and thrombocytosis.
Objective
This study aimed to evaluate serum sclerostin in T2DM and its correlations with bone metabolism and thrombocytosis.
Patients and methods
Fifty male T2DM patients were enrolled; they were divided into two groups according to existing thrombocytosis. Forty age-matched men were included as controls. Clinical tests of physical mobility, fasting blood glucose, glycated hemoglobin, calcium, creatinine, parathormone (PTH), 25-hydroxyvitamin D, bone-specific alkaline phosphatase (BALP), serum carboxy-terminal cross-linked telopeptide of type I collagen (sCTX-I), serum sclerostin, and BMD were performed.
Results
There were insignificant increases in BMD in diabetic patients versus controls. There were significantly lower levels of PTH, BALP, and sCTX-I in the diabetes mellitus (DM) patient groups compared with the controls (P < 0.001). Serum sclerostin levels were significantly higher in DM patients than the controls, with insignificantly higher sclerostin levels in group II. Serum sclerostin was correlated positively with disease duration and correlated negatively with PTH, BALP, and sCTX-I (P < 0.001).
Conclusion
Sclerostin plays a role in the pathogenesis of bone changes in T2DM. The interplay between vitamin D, PTH, and blood glucose highlights the possibility of an existing endocrine axis. Finally, the role of osteocytes in regulating hematopoiesis and association with DM and osteoporosis should be investigated further.